Generation of hemangioblasts from human pluripotent stem cells

Abstract

Hemangioblasts are progenitors with the capacity to differentiate into hematopoietic, endothelial, smooth muscle, and mesenchymal stromal cells and represent an excellent candidate of cell therapy for a variety of human diseases. To realize their clinical potential, first, an efficient and controlled differentiation toward hemangioblasts in a scalable manner, probably in a bioreactor setting, from an unlimited source is required. These cells also need to be generated under animal components and cell-free conditions, or additional regulatory challenges, such as xeno-transplant, will have to be addressed. The ability of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSC) to divide indefinitely without losing pluripotency may allow them to serve as an inexhaustible source for the large-scale production of therapeutic cells. In this chapter, we describe a robust system that can efficiently generate large numbers of hemangioblasts from multiple hESCs and iPSC lines under well-defined conditions, which is an important step for future clinical applications, with the potential of developing a GMP-compatible scalable system.